Gastroenterology - Haemochromatosis, Wilson's Disease, Alpha 1 Antitrypsin deficiency Flashcards
Haemochromatosis - what is it?
It is a autosomal recessive disorder of iron absorption and metabolism, resulting in iron accumulation
Haemochromatosis - what is it caused by?
Caused by inheritance of mutations in the HFE gene located on both copies of chromosome 6
Haemochromatosis - what are the symptoms?
Early disease - asymptomatic
Presenting symptoms:
- Arthralgia
- Chronic fatigue
- Erectile dysfunction - Fe deposits in gonads
- Pigmentation - bronze/slate-grey
- DM - Fe in pancreas
- Liver cirrhosis - hepatocellular deposition
- Hair loss
- Cognitive - memory and mood disturbances
- Cardiomyopathy
- Chondrocalcinosis - calcium deposits in joints, causing arthritis
Haemochromatosis - what investigations can you do?
Genetic testing for C282Y and H63D mutations
Liver biopsy with PERLs STAIN
Iron study profile
MRI - to see Fe deposits in liver and heart
Haemochromatosis - what would you see on a positive iron study profile?
Raised ferritin (500ug/L) and iron Transferrin saturation >55% in men, >50% in women
Haemochromatosis - management?
1ST LINE - Venesection, weekly blood removal
2ND LINE - Desferrioxamine
Manage and treat complications
Genetic counselling
Wilson’s Disease - what is it?
Autosomal recessive disorder characterised by excessive copper deposits in body tissues
Wilson’s Disease - what abnormalities does the disease cause in the body?
Increased small intestine copper absorption
Decreased hepatic excretion of copper
Wilson’s Disease - where is the defect found on the chromosome?
Defect is found on ATP7B on chromosome 13
Wilson’s Disease - what are the 3 main presenting systems and their features?
Present with 1 or more of 3 system presentations:
LIVER:
1. Chronic hepatitis -> liver cirrhosis
NEUROLOGICAL:
- Concentration disturbance
- Dysarthria
- Dystonia
- Cu depo in Basal Ganglia -> parkinsonism (triad of parkinsons, symmetrical symptoms)
PSYCHIATRIC:
- Mild depression
- Psychosis
Wilson’s Disease - what are some signs?
Kayser-Fleischer Rings - deposits of Cu in the descemet membrane of cornea
Slit Lamp examination
Wilson’s Disease - what are other features?
Haemolytic anaemia
Renal tubular damage
Osteopenia
Wilson’s Disease - diagnosis?
SERUM CAERULOPLASMIN, protein that carries Cu in blood (not specific as can be raised in cancer or inflammation)
Liver biopsy - test for CU content, GOLD STANDARD
24 hour urine Cu assay
Serum Cu -> decreased
Check for Kayser-Fleischer Rings with Slit Lamp
Wilson’s Disease - management
Remove excessive copper from body -> copper chelation:
Penicillamine 1ST LINE
Trientene
Alpha 1 Antitrypsin Deficiency (A1AT) - what is it?
Inherited condition where the PROTEASE INHIBITOR (Pi) alpha 1 antitrypsin is not produced enough by the liver due to a genetic abnormality
Alpha 1 Antitrypsin Deficiency - what is alpha 1 antitrypsin and elastase?
It is a protease inhibitor
Elastase is an enzyme secreted by neutrophils that digests connective tissue
Alpha 1 antitrypsin is produced by liver, travels around body and protects cells by inhibiting the NEUTROPHIL ELASTASE enzyme
Alpha 1 Antitrypsin Deficiency - what chromosome is it coded for on?
Chromosome 14
Alpha 1 Antitrypsin Deficiency - what type of genetic inheritance is it?
Autosomal Recessive
Alpha 1 Antitrypsin Deficiency - what are the two main organs affected and associated diseases?
Liver - Liver cirrhosis
Lungs - Bronchiectasis and emphysema in lungs
Alpha 1 Antitrypsin Deficiency - how does the genetic defect lead to liver cirrhosis?
Alpha 1 antitrypsin made in liver
In AIAD, abnormal version made
Abnormal version gets trapped in liver, builds up, causes liver damage
Damage progresses to cirrhosis
Can lead to hepatocellular carcinoma
Alpha 1 Antitrypsin Deficiency - how does the genetic defect lead to lung problems?
Lack of normal alpha 1 antitrypsin means there is excess of protease enzymes that attack and digest connective tissue in lungs
Leads to emphysema and bronchiectasis over time
Alpha 1 Antitrypsin Deficiency - what investigations can you do?
- AIAT concentrations - LOW
- LIVER BIOPSY - cirrhosis, and acid-Schiff-positive staining globules (stain highlights abnormal A1AT proteins) in hepatocytes
- Genetic screening
- CT thorax for emphysema and bronchiectasis
Alpha 1 Antitrypsin Deficiency - management?
- Symptomatic managment
- No smoking
- IV AIAT protein concentrates
- Surgery - organ transplant